The overall objective of this grant is to study the role of adenosine-3', 5'-phosphate (cyclic AMP) in the regulation of central nervous system function by examining factors controlling cyclic AMP metabolism in CNS tissue. Currently, the project is aimed at characterizing endogenous humoral agents and the corresponding receptors influencing the accumulation of cyclic AMP. Specifically, a search is under way to identify the substances responsible for the ability of 40 mM KCl to promote the accumulation of cyclic AMP in guinea pig cerebral cortical slices incubated in vitro. Elevated K ion concentrations can increase cyclic AMP levels in slices even in the presence of maximal amounts of adenosine and the biogenic amine blocking agent, phenoxy benzamine. Extracts of brain tissue are being examined for their ability to increase cyclic AMP levels in test slices incubated in the presence of adenosine and the blocking agents. BIBLIOGRAPHIC REFERENCES: Regulation of cyclic adenosine 3', 5'-monophosphate levels in guinea pig cerebral cortex by interaction of alpha-adrenergic and adenosine receptor activity. A. Sattin, T.W. Rall and J. Zanella; J. Pharmacol. Expt'l. Ther., 192, 22-32, 1975. On the importance of cyclic AMP in neurobiology: An essay. T.W. Rall, Metabolism 24, 241-248, 1975.